TY - JOUR
T1 - B cell αv integrins regulate TLR-driven autoimmunity
AU - Acharya, Mridu
AU - Raso, Fiona
AU - Sagadiev, Sara
AU - Gilbertson, Emily
AU - Kadavy, Lauren
AU - Li, Quan Z.
AU - Yan, Mei
AU - Stuart, Lynda M.
AU - Hamerman, Jessica A.
AU - Lacy-Hulbert, Adam
N1 - Funding Information:
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) Grant DK093695 (to A.L.-H.) and National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Grants AR076242 and AI150178 (both to J.A.H.).
Publisher Copyright:
Copyright © 2020 by The American Association of Immunologists, Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Systemic lupus erythematosus (SLE) is defined by loss of B cell tolerance, resulting in production of autoantibodies against nucleic acids and other cellular Ags. Aberrant activation of TLRs by self-derived RNA and DNA is strongly associated with SLE in patients and in mouse models, but the mechanism by which TLR signaling to self-ligands is regulated remains poorly understood. In this study, we show that αv integrin plays a critical role in regulating B cell TLR signaling to self-antigens in mice. We show that deletion of αv from B cells accelerates autoantibody production and autoimmune kidney disease in the Tlr7.1 transgenic mouse model of SLE. Increased autoimmunity was associated with specific expansion of transitional B cells, extrafollicular IgG2cproducing plasma cells, and activation of CD4 and CD8 T cells. Our data show that αv-mediated regulation of TLR signaling in B cells is critical for preventing autoimmunity and indicate that loss of αv promotes escape from tolerance. Thus, we identify a new regulatory pathway in autoimmunity and elucidate upstream signals that adjust B cell activation to prevent development of autoimmunity in a mouse model.
AB - Systemic lupus erythematosus (SLE) is defined by loss of B cell tolerance, resulting in production of autoantibodies against nucleic acids and other cellular Ags. Aberrant activation of TLRs by self-derived RNA and DNA is strongly associated with SLE in patients and in mouse models, but the mechanism by which TLR signaling to self-ligands is regulated remains poorly understood. In this study, we show that αv integrin plays a critical role in regulating B cell TLR signaling to self-antigens in mice. We show that deletion of αv from B cells accelerates autoantibody production and autoimmune kidney disease in the Tlr7.1 transgenic mouse model of SLE. Increased autoimmunity was associated with specific expansion of transitional B cells, extrafollicular IgG2cproducing plasma cells, and activation of CD4 and CD8 T cells. Our data show that αv-mediated regulation of TLR signaling in B cells is critical for preventing autoimmunity and indicate that loss of αv promotes escape from tolerance. Thus, we identify a new regulatory pathway in autoimmunity and elucidate upstream signals that adjust B cell activation to prevent development of autoimmunity in a mouse model.
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U2 - 10.4049/jimmunol.1901056
DO - 10.4049/jimmunol.1901056
M3 - Article
C2 - 32859730
AN - SCOPUS:85091469811
SN - 0022-1767
VL - 205
SP - 1810
EP - 1818
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -